6-methoxy-1-benzofuran-2-carbaldehyde

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-methoxybenzofuran-2-carbaldehyde (0.21 g, 1.19 mmol), dimethyl(1-diazo-2-oxopropyl)phosphonate (0.27 g, 1.43 mmol) and K2CO3 (0.33 g, 2.4 mmol) in anhydrous MeOH (5 ml) was stirred overnight at room temperature. The solvent was evaporated and the residue was taken in EtOAc (50 ml), washed with H2O and dried over MgSO4 and filtered. The filtrate was evaporated to dryness to give the crude product (0.18 g; 88%), which was used in the next step without purification. 1H-NMR (CDCl3) 1.53 (s, 1H); 3.82 (s, 3H); 6.87 (dd, 1H, J=2.25, 8.58 Hz), 6.92 (s, 1H); 6.95 (d, 1H, J=2.01 Hz); 7.39 (d, 1H, J=8.61 Hz). The solvent was evaporated washed with H2O dried over MgSO4 filtered The filtrate was evaporated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-methoxybenzofuran-2-carbaldehyde (0.21 g, 1.19 mmol), dimethyl(1-diazo-2-oxopropyl)phosphonate (0.27 g, 1.43 mmol) and K2CO3 (0.33 g, 2.4 mmol) in anhydrous MeOH (5 ml) was stirred overnight at room temperature. The solvent was evaporated and the residue was taken in EtOAc (50 ml), washed with H2O and dried over MgSO4 and filtered. The filtrate was evaporated to dryness to give the crude product (0.18 g; 88%), which was used in the next step without purification. 1H-NMR (CDCl3) 1.53 (s, 1H); 3.82 (s, 3H); 6.87 (dd, 1H, J=2.25, 8.58 Hz), 6.92 (s, 1H); 6.95 (d, 1H, J=2.01 Hz); 7.39 (d, 1H, J=8.61 Hz). The solvent was evaporated washed with H2O dried over MgSO4 filtered The filtrate was evaporated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred slurry LiAlH4 (0.114 g, 3 mmol) in anhydrous Et2O (5 ml) was added drop wise the solution of ethyl-6-methoxybenzofuran-2-carboxylate (0.380 g, 1.73 mmol) and stirring was continued for 0.5 h at room temperature. The reaction mixture was quenched with EtOAc:H2O:MeOH mixture (7:3:1), diluted to 20 ml with EtOAc and filtered through Celite. The filtrate was evaporated and the residue was dried in vacuo to give the creamy paste (0.324 g) which was used as such for next step. This (0.310 g) was dissolved in anhydrous dioxane (10 ml) and MnO2 (1 g, excess) was added to it. The suspension was stirred at reflux for 3 h, cooled to room temperature and filtered through Celite pad. The filtrate was evaporated to dryness and the residue was purified by FCC (SiO2, hexane: EtOAc; 70:30), to give the title compound (0.182 g; 76%), as light pink crystalline solid. 1H-NMR (CDCl3) 3.87 (s, 3H); 6.96 (dd, 1H, J=2.22, 8.73 Hz); 7.03 (d, 1H, J=1.83 Hz); 7.48 (5, 1H); 7.59 (d, 1H, J=8.7 Hz); 9.74 (s, 1H). The reaction mixture was quenched with EtOAc H2O:MeOH mixture (7:3:1), diluted to 20 ml with EtOAc filtered through Celite The filtrate was evaporated the residue was dried in vacuo to give the creamy paste (0.324 g) which The suspension was stirred at reflux for 3 h filtered through Celite pad The filtrate was evaporated to dryness the residue was purified by FCC (SiO2, hexane: EtOAc; 70:30)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An ice-cooled solution of 4.0 g (0.017 mole) of N,6-dimethoxy-N-methyl-2-benzofurancarboxamide in 100 ml of tetrahydrofuran was treated cautiously over 15 minutes (under a nitrogen atmosphere) with 0.65 g (0.017 mole) of lithium aluminum hydride. The mixture was stirred for 1 hour, then quenched by the careful addition of 100 ml of saturated aqueous sodium bisulfate solution. The reaction mixture was extracted with ether (3X 75 ml), and the combined extracts were washed with cold 2% aqueous hydrochloric acid (2X 100 ml), followed by brine (lX 100 ml). The organic layer was dried (anhydrous magnesium sulfate) and evaporated. The residue was chromatographed (silica gel, dichloromethane elution) to yield 2.2 g (74% yield) of the analytically pure aidehyde, mp 75°-77° . quenched by the careful addition of 100 ml of saturated aqueous sodium bisulfate solution The reaction mixture was extracted with ether (3X 75 ml) the combined extracts were washed with cold 2% aqueous hydrochloric acid (2X 100 ml) The organic layer was dried (anhydrous magnesium sulfate) evaporated The residue was chromatographed (silica gel, dichloromethane elution) to yield 2.2 g (74% yield) of the analytically pure aidehyde, mp 75°-77°

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An ice-cooled solution of 4.0 g (0.017 mole) of N,6-dimethoxy-N-methyl-2-benzofurancarboxamide in 100 ml of tetrahydrofuran was treated cautiously over 15 minutes (under a nitrogen atmosphere) with 0.65 g (0.017 mole) of lithium aluminum hydride. The mixture was stirred for 1 hour, then quenched by the careful addition of 100 ml of saturated aqueous sodium bisulfate solution. The reaction mixture was extracted with ether (3X 75 ml), and the combined extracts were washed with cold 2% aqueous hydrochloric acid (2X 100 ml), followed by brine (lX 100 ml). The organic layer was dried (anhydrous magnesium sulfate) and evaporated. The residue was chromatographed (silica gel, dichloromethane elution) to yield 2.2 g (74% yield) of the analytically pure aidehyde, mp 75°-77° . quenched by the careful addition of 100 ml of saturated aqueous sodium bisulfate solution The reaction mixture was extracted with ether (3X 75 ml) the combined extracts were washed with cold 2% aqueous hydrochloric acid (2X 100 ml) The organic layer was dried (anhydrous magnesium sulfate) evaporated The residue was chromatographed (silica gel, dichloromethane elution) to yield 2.2 g (74% yield) of the analytically pure aidehyde, mp 75°-77°

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-methoxybenzofuran-2-carbaldehyde (0.21 g, 1.19 mmol), dimethyl(1-diazo-2-oxopropyl)phosphonate (0.27 g, 1.43 mmol) and K2CO3 (0.33 g, 2.4 mmol) in anhydrous MeOH (5 ml) was stirred overnight at room temperature. The solvent was evaporated and the residue was taken in EtOAc (50 ml), washed with H2O and dried over MgSO4 and filtered. The filtrate was evaporated to dryness to give the crude product (0.18 g; 88%), which was used in the next step without purification. 1H-NMR (CDCl3) 1.53 (s, 1H); 3.82 (s, 3H); 6.87 (dd, 1H, J=2.25, 8.58 Hz), 6.92 (s, 1H); 6.95 (d, 1H, J=2.01 Hz); 7.39 (d, 1H, J=8.61 Hz). The solvent was evaporated washed with H2O dried over MgSO4 filtered The filtrate was evaporated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred slurry LiAlH4 (0.114 g, 3 mmol) in anhydrous Et2O (5 ml) was added drop wise the solution of ethyl-6-methoxybenzofuran-2-carboxylate (0.380 g, 1.73 mmol) and stirring was continued for 0.5 h at room temperature. The reaction mixture was quenched with EtOAc:H2O:MeOH mixture (7:3:1), diluted to 20 ml with EtOAc and filtered through Celite. The filtrate was evaporated and the residue was dried in vacuo to give the creamy paste (0.324 g) which was used as such for next step. This (0.310 g) was dissolved in anhydrous dioxane (10 ml) and MnO2 (1 g, excess) was added to it. The suspension was stirred at reflux for 3 h, cooled to room temperature and filtered through Celite pad. The filtrate was evaporated to dryness and the residue was purified by FCC (SiO2, hexane: EtOAc; 70:30), to give the title compound (0.182 g; 76%), as light pink crystalline solid. 1H-NMR (CDCl3) 3.87 (s, 3H); 6.96 (dd, 1H, J=2.22, 8.73 Hz); 7.03 (d, 1H, J=1.83 Hz); 7.48 (5, 1H); 7.59 (d, 1H, J=8.7 Hz); 9.74 (s, 1H). The reaction mixture was quenched with EtOAc H2O:MeOH mixture (7:3:1), diluted to 20 ml with EtOAc filtered through Celite The filtrate was evaporated the residue was dried in vacuo to give the creamy paste (0.324 g) which The suspension was stirred at reflux for 3 h filtered through Celite pad The filtrate was evaporated to dryness the residue was purified by FCC (SiO2, hexane: EtOAc; 70:30)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An ice-cooled solution of 4.0 g (0.017 mole) of N,6-dimethoxy-N-methyl-2-benzofurancarboxamide in 100 ml of tetrahydrofuran was treated cautiously over 15 minutes (under a nitrogen atmosphere) with 0.65 g (0.017 mole) of lithium aluminum hydride. The mixture was stirred for 1 hour, then quenched by the careful addition of 100 ml of saturated aqueous sodium bisulfate solution. The reaction mixture was extracted with ether (3X 75 ml), and the combined extracts were washed with cold 2% aqueous hydrochloric acid (2X 100 ml), followed by brine (lX 100 ml). The organic layer was dried (anhydrous magnesium sulfate) and evaporated. The residue was chromatographed (silica gel, dichloromethane elution) to yield 2.2 g (74% yield) of the analytically pure aidehyde, mp 75°-77° . quenched by the careful addition of 100 ml of saturated aqueous sodium bisulfate solution The reaction mixture was extracted with ether (3X 75 ml) the combined extracts were washed with cold 2% aqueous hydrochloric acid (2X 100 ml) The organic layer was dried (anhydrous magnesium sulfate) evaporated The residue was chromatographed (silica gel, dichloromethane elution) to yield 2.2 g (74% yield) of the analytically pure aidehyde, mp 75°-77°